ABSTRACT X-Ray mammography has contributed to a reduction in mortality due to breast cancer. It is inherently limited, though, as it is incapable of direct observation of physiological information relevant to the functioning of cancer, which ultimately limits the specificity and prognostic ability of X-Ray mammography. Diffuse optical tomography (or tomographic optical breast imaging) is a promising imaging modality that provides information on the functioning and evolution of cancer - in particular, angiogenesis and hemoglobin oxygen saturation. It suffers, however, from limited spatial resolution relative to X-Ray, and this inhibits structural guidance and interpretation of the images obtained. This obstacle can be overcome by acquiring diffuse optical and X-Ray mammographic images simultaneously - that is, by combining the two modalities in a pioneering effort to overcome their respective limitations, mammography limited by specificity and optical limited by resolution, to produce a new multi-modality imaging method with enhanced specificity and prognostic value. We propose to advance the clinical utility of tomographic optical breast imaging by synergistically fusing the diffuse optical technology with state-of-the-art digital X-Ray mammographic 3D tomography (known as Tomosynthesis), thus producing a multi-modality imaging method that integrates structural and functional information relevant to the screening and diagnosis of breast cancer. We believe that this combination will ultimately allow better differentiation of tumors through angiogenic and metabolic markers known to have prognostic value. During this grant period, we propose to further develop the optical technology and perform a clinical study to explore the optical sensitivity to detecting lesions already indicated by X-Ray, and the optical specificity to identifying malignant lesions as characterized by biopsy. We will also explore imaging tissue dynamic biomarkers such as blood flow and oxygen consumption using time-resolved optical measurement for breast under mammographic compression. This research project would not be feasible without the clinical research expertise of the Breast Imaging Research Lab, headed by Dr. Kopans.